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PPARgamma Antagonists Attenuate Hypoxia‐induced Pulmonary Hypertension
Author(s) -
Crossno Joseph T,
Sullivan Timothy M,
Morris Kenneth G,
Klemm Dwight J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1209.2
Subject(s) - rosiglitazone , agonist , endocrinology , medicine , antagonist , peroxisome proliferator activated receptor , hypoxia (environmental) , right ventricular hypertrophy , muscle hypertrophy , chemistry , receptor , pulmonary hypertension , pharmacology , organic chemistry , oxygen
Rationale: Peroxisome proliferators‐activated receptor γ (PPARγ) agonists attenuate hypoxia (Hx)‐induced pulmonary artery (PA) remodeling. The present study tested the hypothesis that PPARγ antagonists exacerbate Hx‐induced PA remodeling. Methods: Wistar‐Kyoto rats were randomized to normoxia (Nx) and hypobaric Hx and treated with or without the PPARγ agonist Rosiglitazone (ROSI) or the PPARγ antagonists GW9662, T0070907, or SR‐202 for 3 weeks. Results: PA catheterization performed on Hx‐ROSI treated groups had no attenuation of Hx‐pulmonary hypertension (PH) vs Hx‐Controls. However, PPARγ antagonist treatment resulted in a decrease in PA pressures in response to chronic Hx [p < 0.05]. PA morphometric analysis demonstrated a marked decrease in proximal and distal PA remodeling vs Hx‐Controls [p = 0.003]. Right ventricular hypertrophy [RV/(LV+S)] was decreased in both the Hx‐PPARγ agonist and antagonist treated groups [p = 0.05]. The decrease in PA remodeling and RV hypertrophy was due to inhibition of proliferation without an increase in apoptosis. Conclusions: PPARγ antagonists GW9662, T0070907 and SR‐202 exert a significant vascular protective effect on Hx‐induced PH and PA remodeling.